Diagnosing multiple drug hypersensitivity in children

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Multiple drug hypersensitivity (MDH) has been defined as a hypersensitivity to two or more chemically different drugs. Two types of MDH have been reported: the first one, which develops to different drugs administered simultaneously and the second type, in which sensitizations develop sequentially. In children, studies which diagnose MDH on the basis of positive allergologic tests to 2 or more chemically different drugs are lacking.


We conducted a prospective study evaluating children with histories of MDH by skin tests, patch tests, serum-specific IgE assays, and drug provocation tests.


A MDH was diagnosed in 7 (2.5%) of the 279 children evaluated who completed the study. The responsible drugs were β-lactams (penicillins and cephalosporins) in 5 episodes, ibuprofen and anticonvulsants in 3, and erythromycin, fentanyl, methylprednisolone, and cotrimoxazole in 1. Sensitivity to 2 chemically different drugs was diagnosed in 6 children and to 3 drugs in 1 child. Two of the 7 children presented the first type of MDH, whereas 5 displayed the second one.


MDH can occur in children, even to drugs other than antibiotics. It is crucial to evaluate children with histories of MDH using both in vivo and in vitro allergologic tests, including challenges. In fact, such approach allows the physician to confirm the diagnosis of MDH in a small percentage of children with histories of MDH, as well as to rule it out in the great majority of them.

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